In vitro growth inhibition of Plasmodium falciparum by retinol at concentrations present in normal human serum

To assess the in vitro effect of retinol on Plasmodium falciparum, the standard isolates 3D7, D10, W2 and K1 in continuous culture were exposed to retinol added in concentrations ranging from 10−7 to 0.1 μmol/l. Parasite growth inhibition was assessed from 3H-hypoxanthine incorporation. Triplicate experiments were performed at physiological pH and in the case of D10, additional experiments were performed at pH 7.2 and 7.6. Final media retinol concentrations were assayed using high performance liquid chromatography. Retinol inhibited growth of both asynchronous and synchronous cultures of 3D7 and D10 and asynchronous cultures of W2 and K1. IC50 values determined from assayed media concentrations ranged from 0.2 to 3.9 μmol/l and were comparable to concentrations in normal human serum (1.0–3.0 μmol/l). IC50 values for asychronous D10 cultures at pH 7.2 were lower than at pH 7.4 or 7.6 (0.5, 3.9 and 5.0 μmol/l, respectively); results from synchronous cultures were similar. These data suggest that P. falciparum is a retinol-sensitive parasite, especially at pH levels equivalent to those in an acidotic patient. Adjunctive retinol therapy may have a role in clinical management of malaria.